Comparison of four beta-lactamase inhibitors in combination with ampicillin against Mycobacterium tuberculosis

The in-vitro activity of a beta-lactamase inhibitor (clavulanic acid, sulbactam, BL-P2013 or BL-P2090) in combination with ampicillin against 13 isolates of Mycobacterium tuberculosis was determined by broth dilution. The agents were tested in 1:1 molar ratio of ampicillin to beta-lactamase inhibitor. The beta-lactamase inhibitors alone did not inhibit growth at the highest concentration tested. The MIC90 for ampicillin alone was greater than 32 mg/l. Clavulanic acid plus ampicillin was the most active combination with an MIC90 of 11 microM (4 mg/l of ampicillin). The MIC90 of ampicillin in combination with sulbactam, BL-P2013 or BL-P2090 was 23 microM (8 mg/l of ampicillin). A 1:1 ratio of ampicillin to inhibitor was more active than was a 2:1 ratio. The addition of a beta-lactamase inhibitor to ampicillin greatly improves its in-vitro activity against M. tuberculosis.